The objective of this project is to examine the physiological and pharmacological mechanisms involved in the centrifugal regulation of primary afferent input. This work is being pursued, in the current program, at two levels. 1) The regulation of afferent terminal polarization by neuronal systems in the dorsal horn with respect to various putative transmitters present in this structure. At present the focus is on norepinephrine, serotonin and tryptamine. 2) The effects of antidromic invasion on the responsiveness of sensory receptors will also be investigated. This work is being pursued primarily in the rat preparation using single unit or multiple unit recordings from dorsal root filaments. Transmitters systems are being investigated by pharmacological manipulation.